This funding opportunity announcement builds on the
National Institute of Nursing Research’s (NINR’s) previous efforts to
understand the mechanisms related to preterm birth by leveraging the work
performed by the National Institutes of Health’s (NIH’s) Human Microbiome
Project (HMP). NINR seeks research to address the contribution of the
microbiome to preterm labor and delivery. Preterm birth is a leading cause
of neonatal mortality and morbidity, and evidence suggests that although
there are multiple contributors, microorganisms may play a significant role.
Research conducted as part of the HMP demonstrated that a shift in bacterial
species occurs in women during the course of a pregnancy. An enhanced
knowledge of the microbiome, the changes that are associated with increased
risk for preterm labor and delivery, and the influence of genetic and
environmental factors is needed to better address this important public
health issue. Interdisciplinary collaborations that include nurse scientists
in the project team are strongly encouraged. Additionally, applicants should
consider engaging the resources and expertise of nearby or otherwise
available Clinical and Translational Science Award grant sites (CTSAs) and/or
federally funded research centers where possible.

Key Dates

Posted Date

February 11, 2013

Open Date (Earliest Submission Date)

April 9, 2013

Letter of Intent Due Date(s)

April 9, 2013

Application Due Date(s)

May 9, 2013, by 5:00 PM local time of applicant
organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June/July 2013

Advisory Council Review

August 2013

Earliest Start Date

September 1, 2013

Expiration Date

May 10, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

This funding opportunity announcement seeks research
addressing the underlying mechanisms related to preterm labor and delivery by
focusing on the role that the microbiome plays in predisposing women to this
condition. An enhanced knowledge of the microbiome, the changes that are
associated with increased risk for preterm labor and delivery, and the
influence of genetic and environmental factors is needed to better inform the
search for effective prevention strategies. Examination of the human microbiome
has changed the way we think about disease and health. The human microbiome is
the full collection of microbes and their genomes that naturally exist within
various habitats of the human body. These microbes, which are essential for
maintaining health, play a role in digesting food, absorbing nutrients,
producing vitamins and anti-inflammatories, and conferring protection from
disease (such as infections). NIH’s Human Microbiome Project (HMP), established
by the Common Fund in 2007, aims to characterize the microbial communities
found on several sites (including nasal passages, oral cavities, skin,
gastrointestinal tract, urogenital tract) on the human body in addition to the
role these microbes play in human health and disease. Recent advances in
metagenomics have provided a high-throughput means to study the microorganisms
at the DNA level, providing an unprecedented window into the ability of
microbes to cause disease as well as protect the host. For example, sequencing
of the microbial 16S rRNA gene has provided in-depth information about
microbial diversity that cannot be discerned using traditional cultivation methods.

The microbiome can be influenced by genetics, nutrition,
environment, lifestyle, medications, and other host factors. The vaginal
microbiome varies widely among healthy, asymptomatic women of reproductive age,
and studies have additionally shown that the vaginal bacterial community
composition varies among different ethnic groups. Studies of the vaginal
microbiome in pregnant and non-pregnant women revealed that the vaginal
bacterial community naturally undergoes marked decrease in species diversity as
the pregnancy progresses. Changes in the diversity of gut bacteria during
pregnancy have also been shown to occur. The biological significance of these
findings as well as their role in conferring risk for, or alternatively
protection from, intra-uterine bacterial invasion leading to preterm labor and
delivery requires further investigation.

Although there are multiple contributors, evidence suggests
that bacterial colonization of the normally sterile intra-uterine environment
may be responsible for as many as 40% of preterm births. There are several
potential sites of bacterial infection within the gravid uterus, including the
choriodecidual space, within the fetal membranes, and within the placenta, the
amniotic fluid, or the umbilical cord of the fetus. Microorganisms can enter
the amniotic cavity through various routes, but the most common pathway is
ascending from the vagina and cervix. Bacterial vaginosis (BV) affects
approximately 15% of women of reproductive age and is a known risk factor for
preterm labor and delivery in addition to late miscarriages. BV occurs as a
result of a shift in the vaginal microbial community and is associated with
genital tract infections as well as pregnancy complications. The etiology of
BV is essentially unknown, and prophylactic treatment for BV has not led to a
reduction in preterm birth in the general population. Recent evidence of an
increased risk for spontaneous preterm birth resulting from an association
between BV and polymorphisms in inflammatory response genes further
demonstrates the multifactorial nature of this problem. Additionally, although
research has primarily focused on bacteria originating from genital infections,
there is evidence that various non-genital tract infections, such as
pyelonephritis and asymptomatic bacteriuria, pneumonia, periodontal disease,
and appendicitis, in addition to bacteria associated with the skin, fecal, and
gut microbiota may also predispose to preterm birth. A greater understanding
of these factors and phenomena is needed.

Preterm birth, which is defined as births before 37 weeks of
gestation, is the leading cause of neonatal mortality worldwide. Preterm
infants are at increased risk of life-long disability, poor health, and early
death compared with infants born later in pregnancy. The U.S. preterm birth
rate rose by more than one-third from the early 1980s through 2006, when it
reached 12.8 percent. The 2009 preterm birth rate was 12.18 percent (Centers
for Disease Control and Prevention’s National Center for Health Statistics, 2011).
The rate of preterm birth varies among different racial and ethnic groups;
however, this disparity cannot be explained by socioeconomic conditions or
maternal behaviors. A report by the Institute of Medicine estimated that the
annual societal economic burden associated with preterm birth in the U.S. was
at least $26 billion in 2005, or approximately $51,600 per infant born preterm,
not including the cost of medical care beyond early childhood or caretaker
costs (http://www.iom.edu/~/media/Files/Report%20Files/2006/Preterm-Birth-Causes-Consequences-and-Prevention/Preterm%20Birth%202006%20Report%20Brief.pdf).

An enhanced knowledge of the microbiome, the perturbations
in the microbiome that are associated with risk for preterm labor and delivery,
and the influence of genetic and environmental factors is needed to better
address this important public health problem. The goal of this funding
opportunity announcement is to build on the Human Microbiome Project as well as
other research related to this topic.

Research
Objectives:

While there is evidence that the microbiome undergoes alterations
during pregnancy and is influenced by diet, medication, and other factors, the
impact of these factors in predisposing women to preterm labor and delivery has
not been well-studied. Research topics to be addressed include, but are not
limited to:

Types, location, and influence of bacteria found in women who
experience preterm labor and delivery

Symptoms associated with changes in the microbiome in women who
experience preterm labor and delivery

Genomic and epigenomic variants that potentially interact or
associate with the microbiome in predisposing women to preterm labor and
delivery

Biomarkers that reflect changes in the woman’s microbiome and can
be used as indicators of risk for preterm labor and delivery

Physiological, environmental, and social and behavioral factors
that potentially influence the microbiome in predisposing women to preterm
labor and delivery

Role of comorbidities in altering the woman’s microbiome and
increasing the risk for preterm labor and delivery

Interventions that shift the woman’s microbiome toward more
protective states in order to reduce the risk for preterm labor and delivery

Mechanisms related to host inflammatory response to bacterial
invasion and perturbations in the microbiome leading to increased risk for
preterm labor and delivery

Role of different sociodemographic factors (such as geography,
culture, race, ethnicity, etc.) that potentially influence the microbiome in
predisposing women to preterm labor and delivery

Interdisciplinary collaborations that include nurse
scientists in the project team are strongly encouraged. Additionally,
applicants should consider engaging the resources and expertise of nearby or
otherwise available Clinical and Translational Science Award grant sites
(CTSAs) and/or federally funded research centers where possible.

Section II. Award Information

Funding Instrument

Grant: A support mechanism
providing money, property, or both to an eligible entity to carry out an
approved project or activity.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

NINR intends to commit an estimated $2 million, for up
to six awards, split between this FOA and the parallel FOA of identical
scope, RFA-NR-13-003 for FY 2013, contingent on available funds.

Award Budget

Application budgets are limited to $350,000 in direct
costs in any year, not including consortium F&A costs.

Award Project Period

The total project period for an application submitted in
response to this funding opportunity may not exceed 5 years.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete the following registrations
as described in the SF424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

System for
Award Management (SAM)– must maintain an active entity registration
(formerly CCR registration), to be renewed at least annually. Use the Sam.gov
“Manage Entity” function to manage your entity registrations. See the Grants
Registration User Guide at SAM.gov for additional information.

All Program Directors/Principal Investigators (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 6 weeks prior to the application due date.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
submission of applications for this FOA. Follow all instructions in the SF424
(R&R) Application Guide to ensure you complete all appropriate “optional”
components.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications,
regardless of the amount of direct costs requested for any one year should
address a Data Sharing Plan.

Appendix

Do not use the Appendix to circumvent page limits. Follow
all instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.

Applicants
are responsible for viewing their application before the deadline in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management (SAM). Additional information
may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by the
National Institute of Nursing Research, NIH. Applications that are incomplete and/or
nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and injury
to that which is unavoidable in the conduct of scientifically sound research
including the use of analgesic, anesthetic, and tranquilizing drugs and/or
comfortable restraining devices; and 5) methods of euthanasia and reason for
selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Nursing Research, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds
with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a
second level of review by the National Advisory Council on Nursing Research. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH Grants
Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.